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Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage

  • Laboratory Investigation - Human-Animal Tissue
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Abstract

Alkylating agents, commonly used for brain tumor therapy, induce DNA and RNA lesions that, if not repaired, drive cells to apoptosis. Thus, cellular mechanisms that are responsible for nucleic acid repair are possibly involved in drug resistance. This work analyzes hABH2 and hABH3, two human Fe(II)-dependent dioxygenases in pediatric brain tumors that are treated with alkylating agents. We analyzed 25 brain tumor samples for hABH2 and hABH3 mutations; a subset of samples was tested for quantitative expression with Real-Time PCR. Sequencing analysis showed two new mutations in two glioma patients, one of hABH2 coding sequence (I141 V) and the other of hABH3 (D189 N). The mutation at codon 189 falls in a crucial region of the protein. All subjects analyzed by Real-Time PCR showed an enhanced expression of the two genes, particularly of hABH2. This is the first study of hABH2 and hABH3 in pediatric brain tumors; further molecular investigations of their mutations and expression may help determine their role in response to chemotherapy.

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Acknowledgments

We are grateful to Mr. Pasquale Tulimiero for his skilful technical assistance and to Dr. Elisabeth Wheeler (MA) for her language revision. This work was supported by a grant from Associazione Italiana per la Ricerca sul Cancro and Associazione Genitori contro le Leucemie e Tumori Infantili “NOI PER VOI”, “A. Meyer” Children’s Hospital, Florence, Italy.

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Authors and Affiliations

  1. Onco-Hematology Unit, Department of Pediatrics, Florence Medical School, A. Meyer Children’s Hospital, viale Pieraccini 24, 50139, Florence, Italy

    Valentina Cetica, Gabriella Bernini & Iacopo Sardi

  2. Neuro-Surgery Unit, Department of Pediatrics, Florence University Medical School, A. Meyer Children’s Hospital, 50139, Florence, Italy

    Lorenzo Genitori & Massimiliano Sanzo

  3. Medical Genetics Unit, Department of Pediatrics, Florence University Medical School, A. Meyer Children’s Hospital, 50139, Florence, Italy

    Laura Giunti

  4. Pediatric Oncology Unit, Istituto Nazionale Tumori, 20133, Milan, Italy

    Maura Massimino

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  1. Valentina Cetica
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  2. Lorenzo Genitori
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  3. Laura Giunti
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  4. Massimiliano Sanzo
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  5. Gabriella Bernini
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  6. Maura Massimino
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  7. Iacopo Sardi
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Correspondence to Valentina Cetica.

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Cetica, V., Genitori, L., Giunti, L. et al. Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage. J Neurooncol 94, 195–201 (2009). https://doi.org/10.1007/s11060-009-9837-0

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  • DOI: https://doi.org/10.1007/s11060-009-9837-0

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